In PHP, there is resistance to the action of parathyroid hormone with hypocalcemia, hyperphosphatemia, and elevated PTH levels, but PPHP has no biochemical abnormality with normal calcium and phosphorus levels and a normal response to PTH secretion. Both have clinical features of Albright hereditary osteodystrophy. Pseudohypoparathyroidism (PHP) and Pseudo-pseudohypoparathyroidism (PPHP): Both are phenotypic variants with autosomal dominant inheritance with mutation of the GNAS gene. Hypoparathyroidism: Idiopathic (absence, fatty replacement or atrophy of parathyroid gland) or secondary (due to inadvertent removal during thyroidectomy) In a review of 150 cases of Fahr syndrome, 35 (23.3%) had idiopathic hypoparathyroidism, and 23 (15.3%) had secondary (post-thyroidectomy) hypoparathyroidism. Reduced levels of actions of PTH cause hyperphosphatemia and hypocalcemia, which promotes calcification. Parathyroid hormone (PTH) disturbances are the most common cause of bilateral basal ganglia calcifications. (F) Surveillance: Annual neurologic and neuropsychiatric assessment.īasal ganglia calcifications occur in several other familial and non-familial conditions that are required to be excluded before making a diagnosis of primary familial basal ganglia calcification. Prenatal testing and preimplantation genetic diagnosis are possible for high-risk pregnancy in which PDGFB, PDGFRB, XPR1, SLC20A2 pathogenic variant has been detected in the proband. Testing is usually not recommended in individuals <18 years considering social issues, discrimination and anxiety in future, negative impact on parent-child or sibling-child relationship, and uncertain CT scan predictability as penetrance is age-dependent. Testing individuals >18 years can help them in decision making in regards to their marriage, family planning, career, and finance. Predictive testing in the form of brain CT scan (calcium deposits precede clinical manifestations by years) and molecular testing (if PDGFB, PDGFRB, XPR1, SLC20A2 pathogenic variant has been identified in proband) can be offered to asymptomatic first-degree relatives (>18 years) after weighing the ethical and psychosocial conditions because no curative treatment is available. There are no demonstrated medical benefits for screening the relatives. Sometimes the family history of a patient is negative because of the early death of a parent before the disease became evident, or it may have a late-onset in the parent or reduced penetrance. The family history is not fully conclusive. The disease is transmitted in an autosomal dominant fashion. Symptomatic improvement: Relaxation techniques for anxiety, deep brain stimulation for hyperkinetic disorders, soft tissue release for spasticity, or sensory stimulation in basal ganglia dysfunction. Since, some genes have been implicated in Fahr disease, the term idiopathic basal ganglia calcification, used previously, should be avoided. Other loci that have been linked to Fahr disease include IBGC1 locus at chromosome 14q, a locus at chromosome 2q, and another one at chromosome 8. 46% of cases have some unknown gene mutations. There are four genes which have been implicated as the molecular basis of Fahr disease i.e., loss of function mutation in the gene SLC20A2 encoding type 3 sodium-dependent phosphate transporter 2 (PiT2) on chromosome 8p (40%), a mutation in gene XPR1 that encodes for a retroviral receptor with phosphate export function on chromosome 1q (2%), a mutation in the gene which encodes the receptor for members of the platelet-derived growth factor family- gene PDGFRB on chromosome 5q (2%), and gene PDGFB on chromosome 22q (11%). Some studies have reported the phenomenon of anticipation in this disease. Fahr disease is most commonly found to be inherited in an autosomal dominant pattern with incomplete and age-related penetrance, but it may also be transmitted as an autosomal recessive trait or occur sporadically.
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