Endocrine, nutritional and metabolic diseases
Metabolic disorders
Autosomal recessive
12q12-q14
Vitamin D-dependent rickets type II (VDDR II) is an autosomal recessive disorder resulting from the defective response of vitamin D receptors (VDR) in the target tissues to the active hormonal form of vitamin D. Vitamin D is important for enhancing the absorption of calcium from the small intestine and for normal bone development. VDDR II is characterized by the early onset of rickets, alopecia, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated 1,25-(OH)2D3 levels.
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 277440.1.1 | Lebanon | Male | Yes | Yes | Hypocalcemia ; Spasticity ; Bilateral ... Hypocalcemia ; Spasticity ; Bilateral tonic-clonic seizure with generalized onset ; Osteoporosis ; Metaphyseal irregularity ; Respiratory tract infection ; Pneumonia ; Cardiac arrest ; Death in childhood ; Normal scalp hair growth  | NM_001017535.1:c.1190A>C | Homozygous | Autosomal, Recessive | Andary et al, 2017 | Proband |
| 277440.2.1 | Lebanon | Female | Yes | Yes | Hypocalcemia ; Rickets ; Alopecia ; W... Hypocalcemia ; Rickets ; Alopecia ; Waddling gait ; Metaphyseal irregularity | NM_001017535.1:c.1171C>A | Homozygous | Autosomal, Recessive | Andary et al, 2017 | Proband |
| 277440.3.1 | Lebanon | Male | Yes | Yes | Hypocalcemia ; Alopecia totalis ; Bila... Hypocalcemia ; Alopecia totalis ; Bilateral tonic-clonic seizure with generalized onset ; Subcutaneous nodule ; Broad carpal bones ; Bowing of the legs ; Rachitic rosary | NM_001017535.1:c.1171C>A | Homozygous | Autosomal, Recessive | Andary et al, 2017 | Proband |
| 277440.3.2 | Lebanon | Female | Yes | Yes | Hypocalcemia ; Alopecia totalis ; Broa... Hypocalcemia ; Alopecia totalis ; Broad carpal bones | NM_001017535.1:c.1171C>A | Homozygous | Autosomal, Recessive | Andary et al, 2017 | Sister of 277440.3.1 |
| 277440.4.1 | Saudi Arabia | Male | Yes | Yes | Hypocalcemia ; Rickets ; Alopecia ; H... Hypocalcemia ; Rickets ; Alopecia ; Hypophosphatemia ; Secondary hyperparathyroidism | NM_001364085.1:c.137G>T | Homozygous | Autosomal, Recessive | Lin et al. 1996 | Proband |
| 277440.5.1 | United Arab Emirates | Male | Yes | Yes | Hypocalcemia ; Broad carpal bones ; Ra... Hypocalcemia ; Broad carpal bones ; Rachitic rosary ; Rickets ; Respiratory tract infection ; Hypophosphatemia | NM_000376.3:c.821G>A | Homozygous | Autosomal, Recessive | Aljubeh et al. 2011 | Proband |
| 277440.6.1 | United Arab Emirates | Female | No | No | Hypocalcemia ; Rickets ; Broad carpal ... Hypocalcemia ; Rickets ; Broad carpal bones ; Failure to thrive; Respiratory tract infection ; Motor delay ; Frontal bossing ; Hypophosphatemia ; Proptosis; Rachitic rosary ; Generalized hypotonia | NM_000376.3:c.821G>A | Homozygous | Autosomal, Recessive | Aljubeh et al. 2011 |
Khan et al, 1996 were the first to report vitamin D-dependent rickets type II (VDDR II) in a consanguineous Bahraini family.
[Khan IM, Al-Hermi B, Al-Abbasi AJ, Al-Rufai M, Al-Arrayed S. Hereditary 1,25-dihydroxyvitamin D-resistant rickets: a report of several cases in a kindred. Bahrain Med Bull. 1996; 18(1):28-30.]
Al Anzy et al, 1998 described the clinical features of three siblings with clinically different severity of vitamin D dependent rikets type II with alopecia.
[Al-Anzy HM, Alsaleh QA, Salem MT, Nadi H, Sameer E. A new variant of 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia associated with mental retardation and hearing loss. Gulf J Dermatol. 1998; 5(1):30-1.]
Paul and Al-Khusaiby, 1987 reported vitamin D dependent rickets with alopecia in an 18-month-old Omani male born to non-consanguineous parents.
[Paul G, Al-Khusaiby SBM. Vitamin D dependent rickets type II with alopecia. Medical Newsletter. 1987; 3(3):2-6.]
Al-Khenaizan and Vitale, 2003 report two Saudi brothers with vitamin D-dependent rickets type II disease associated with alopecia of the scalp or the body.