| Hypoparathyroidism
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Inheritance
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Gene mutation
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Clinical features
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| Autoimmune[1]
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Autoimmune polyglandular hypoparathyroidism
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Autoimmune polyglandular endocrinopathy type 1
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Autosomal recessive
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Mutation in AIRE gene
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- Also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).
- Presents with a variable combination of:
- Failure of the parathyroid glands, adrenal cortex, gonads, pancreatic beta cells, gastric parietal cells, and thyroid gland, and hepatitis
- Chronic mucocutaneous candidiasis
- Dystrophy of dental enamel and nails, alopecia, vitiligo, and keratopath
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| Isolated
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Familial Isolated hypoparathyroidism
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Autosomal dominant
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PTH gene[2]
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
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| GCM2 gene[3]
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
- Dominant negative mutation
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| Autosomal recessive
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PTH gene[4]
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
|
| GCM2 gene[3][5]
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
|
| X-linked
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FHL1 gene (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27.[6]
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
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| Autosomal dominant hypercalcemia[7]
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Autosomal dominant hypocalcemia type 1
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Autosomal dominant
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Calcium-sensing receptor gene mutation
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- Calcium-sensing receptor gene activating mutation.
- Most common genetic form of hypoparathyroidism.
- Also known as familial hypercalciuric hypocalcemia.
- The activating mutation results in gain in function.
- Calcium-sensing receptor gene activating mutation can also cause Bartter syndrome type 5.This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney.[8][9]
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| Autosomal dominant hypocalcemia type 2
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Autosomal dominant
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G protein G11 (GNA11) mutation
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- Clinical features of hypocalcemia including
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
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| Congenital multisystem syndromes
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DiGeorge syndrome[10]
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Autosomal dominant
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22q11.2 deletion.
|
- Also known as 22q11.2DS, CATCH 22 syndrome, Cayler cardiofacial syndrome, conotruncal anomaly face syndrome (CTAF), deletion 22q11.2 syndrome, Sedlackova syndrome, Shprintzen syndrome, VCFS, velocardiofacial syndrome, and velo-cardio-facial syndrome.
- CATCH 22 stands for cardiac defects, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q11.2 deletion.
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| CHARGE syndrome[11]
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Autosomal dominant
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CHD7 G744S missense mutation
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| Kenny-Caffey syndrome type 1[12]
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Autosomal recessive
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Deletion of the TBCE gene
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- Presents with hypoparathyroidism due to absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones.
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| Kenny-Caffey syndrome type 2[13]
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Autosomal dominant
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Mutation of “family with sequence similarity 111, member A″ (FAM111A) gene located on chromosome locus 11q12.1
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- Patients with Kenny-Caffey sundrome type 2 have same clinical features as Kenny-Caffey syndrome type 1 except for mental retardation.
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| Sanjad-Sakati syndrome[14]
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Autosomal recessive
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Mutation in TBCE gene.
|
|
| Barakat syndrome[15][16]
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Autosomal recessive
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Mutations in the GATA3 gene
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- Also known as hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome
- Presents with primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis.
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| Metabolic diseases
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Mitochondiral polyneuropathies[17]
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Kearns–Sayre syndrome
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Mitochondrial inheritence
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mtDNA deletion
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- Progressive external ophthalmoplegia
- Retinitis pigmentosa
- Cardiomyopathy,
- Heart block
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| Maternally inherited diabetes and deafness (MIDD)
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Mitochondrial inheritence
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MT‑TL1
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- Diabetes mellitus and deafness
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| Mitochondrial enzyme deficiencies
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Mitochondrial trifunctional protein deficiency (MTP deficiency)[18][19]
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Autosomal recessive
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HADHA or HADHB gene mutation
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- Clinical features of mitochondrial trifunctional protein deficiency occurring during infancy include feeding difficulties, lethargy, hypoglycemia, hypotonia, and liver problems.
- Infants with mitochondrial trifunctional protein deficiency are also at high risk for serious heart problems, breathing difficulties, coma, and sudden death.
- Clinical features of mitochondrial trifunctional protein deficiency occurring after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and a loss of sensation in the extremities (peripheral neuropathy).
|
| Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHAD deficiency)[20]
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Autosomal recessive
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G1528C gene mutation
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- Hypoglycemia
- Hepatopathy
- Hypotonia
- Cardiomyopathy
- Retinopathy
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| Heavy metal storage disorders
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Hemochromatosis[21][22]
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Autosomal recessive
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HFE gene mutation
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- Early symptoms of hereditary hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive.
- Late stage clinical fearures may include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration.
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| Wilson's disease[23][24]
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Autosomal recessive
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ATP7B gene mutation
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- Initial features include liver disease in children and young adults.
- Initial features include nervous systems and psychiatric problems in adults.
- Other clinical features include clumsiness, tremors, difficulty walking, speech problems, impaired thinking ability, depression, anxiety, and mood swings.
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