Cognitive and behavioral phenotype of children with pseudohypoparathyroidism type 1A.

Pseudohypoparathyroidism 1A (PHP1A) is a rare, genetic disorder. Most patients with PHP1A have cognitive impairment but this has not been systematically studied. We hypothesized that children with PHP1A would have lower intelligent quotient (IQ) scores than controls. To evaluate cognition and behavior, we prospectively enrolled children with PHP1A, one unaffected sibling (when available) and controls matched on BMI/age/gender/race. Evaluations included cognitive and executive function testing. Parents completed questionnaires on behavior and executive function. We enrolled 16 patients with PHP1A, 8 unaffected siblings, and 15 controls. Results are presented as mean (SD). The PHP1A group had a composite IQ of 85.9 (17.2); 25% had a composite IQ < -2 SD. The PHP1A group had significantly lower IQs than matched controls (composite IQ -17.3, 95%CI -28.1 to -6.5, p < 0.01) and unaffected siblings (composite IQ -21.5, 95%CI -33.9 to -9.1, p < 0.01). Special education services were utilized for 93% of the patients with PHP1A. Deficits were observed in executive function and parents reported delayed adaptive behavior skills and increased rates of attention deficit hyperactivity disorder. In conclusion, children with PHP1A have lower intelligence quotient scores, poorer executive function, delayed adaptive behavior skills, and increased behavior problems.

[Neuropsychiatric symptoms revealing pseudohypoparathyroidism with Fahr's syndrome]. / Manifestations neuropsychiatriques révélant une pseudohypoparathyroïdie avec un syndrome de Fahr.

UNLABELLED: Fahr's syndrome is characterized by the presence of intracerebral, bilateral and symmetrical non-arteriosclerotic calcifications, located in the central grey nuclei. One of its main etiologies is pseudohypoparathyroidism (PHP), due to a resistance to the action of parathormone (PTH) with essentially hypocalcaemia and a normal or a high rate of PTH. CASE REPORT: Mr B.A. is a 36-year-old man, admitted to hospital because of refractory psychotic symptoms associated with alcohol abuse and fits of convulsion, for diagnostic and therapeutic update. Mr B.A. had presented convulsions since the age of 10, without regular medical treatment. He showed a decrease in his school performances and started using alcohol. Since the age of 17, he began expressing delusions of persecution and of enchantment fed by the persistence of the convulsions. He was administered phenobarbital, and classic antipsychotics (haloperidol and levomepromazine) and developed serious extrapyramidal side effects, treated with an anticholinergic (trihexyphenidyl). Evolution was rather disadvantageous: more epileptic fits, exaggeration of tremors; abuse of alcohol and persistence of psychotic symptoms. On admission, psychiatric examination objectified paranoid delusions of being possessed and persecuted by others. Neurological examination revealed the presence of limb tremors, with a positive Froment's sign on the right, and dysarthria. Other than this, the patient was shorter in comparison with his siblings and exhibited bad dentition. A CT brain scan found bilateral, symmetric basal ganglia calcifications, confirmed by MRI, in favour of Fahr's syndrome. Phosphocalcic investigations revealed a low concentration of serum calcium (65 mg/l) and a hyperphosphataemia (60.1mg/l). The blood level of parathyroid hormone was in the upper limit of normal (66 ng/l), and levels of thyroid hormones and thyroid-stimulating hormone were normal. The diagnosis of Fahr's syndrome, revealing a pseudohypoparathyroidism was posed, and the patient was orientated to endocrinology after readjustment in his therapy (sodium valproate and olanzapine). DISCUSSION: About 40% of the patients with Fahr's syndrome are seen with primarily cognitive and other psychiatric findings. For this patient, hypocalcaemia was at the origin of his convulsions, and the use of phenobarbital, known for its hypocalcemiant action, provoked the inverse result. Alcohol drinking also aggravated hypocalcaemia, and maintained the fits. The use of classic antipsychotics and anticholinergic agents, amplified the extrapyramidal signs caused by Fahr's syndrome. Recognizing the origin of the symptoms allowed rethinking the therapeutic strategy according to all these elements. CONCLUSION: Psychiatrists should consider Fahr's syndrome as a differential diagnosis in the evaluation of psychosis associated with convulsions. This case, along with others in the literature, further emphasizes the importance of the role of neuro-imaging and the search for disrupted phosphocalcic metabolism in patients with atypical or refractory psychotic symptoms.

Different subtypes of pseudohypoparathyroidism in the same family with an unusual psychiatric presentation of the index case.

A 13 year old Asian girl presenting with apparent hysterical paralysis and subsequent rapid cycling bipolar mood disorder was found to have biochemical evidence of pseudohypoparathyroidism type II. The mood disorder responded to treatment of the pseudohypoparathyroidism with a vitamin D analogue. Investigation of her parents and siblings showed phenotypes consistent with two distinct types of pseudohypoparathyroidism (type I and type II) in different family members.

Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency.

Pseudohypoparathyroidism type I is a hereditary disorder characterized by resistance to parathyroid hormone and other hormones that work via cyclic adenosine 3', 5'-monophosphate (cAMP). Most patients with this disorder have generalized deficient activity of Ns-protein (type Ia), which couples stimulatory hormone receptors to catalytic adenylate cyclase. In patients with normal Ns-protein activity (type Ib), a decreased incidence of resistance to hormones other than parathyroid hormone exists. Mental deficiency of unknown cause occurs in 47% to 75% of all patients with pseudohypoparathyroidism type I. Because mutations in the adenylate cyclase-cAMP system may affect the learning ability of Drosophila flies, we assessed mental deficiency in 25 patients whose Ns-protein activity we had determined: 9 of 14 patients with type Ia disorder and 0 of 11 patients with type Ib disorder had mental deficiency. We suggest that Ns-protein deficiency, reduced cAMP levels, or both, are involved in the mental deficiency in these patients and probably in mental function in humans.