- Cystinosis (liginac Syndrome).

Cystinosis (liginac Syndrome)

A/E:  defect in the metabolism of cysteine that results in accumulation of cystine crystals in most of the major organs of the body, notably the kidney, liver, eye, and brain.

Incidence:

-       It occurs at an incidence of 1 : 100,000 to 1 : 200,000.

-       Is the most common cause of Fanconi syndrome in children.

-       In certain populations, such as French Canadians, the incidence is much higher.

clinical patterns:

1.    Infantile or nephropathic cystinosis: the most severe form present in the 1st 2 yr of life with severe tubular dysfunction and growth failure. If the disease is not treated, the children develop end-stage renal disease by the end of their 1^st decade.

2.    A milder form of the disease manifests in adolescents and is characterized by less-severe tubular abnormalities and a slower progression to renal failure.

3.    A benign adult form with no renal involvement also exists.

-  Patients with nephropathic cystinosis present with clinical manifestations reflecting their pronounced tubular dysfunction and Fanconi syndrome…?

-  Patients are typically fair skinned and blond because of diminished pigmentation.

-  Ocular presentations include photophobia, retinopathy, and impaired visual acuity.

-  Patients also can develop hypothyroidism, HSM, and delayed sexual maturation.

-  With progressive tubulointerstitial fibrosis, renal insufficiency is invariant.

Diagnosis:

- Detection of cysteine crystals in the cornea  by slit lamp.

- Increased white blood cell (WBC) cystine levels are diagnostic.

-  Prenatal testing is available for at-risk families.

Treatment :

-   correcting the metabolic abnormalities associated with Fanconi syndrome or chronic renal failure.

-   In addition, specific therapy is available with cysteamine, which binds to cystine and converts it to cysteine. This facilitates lysosomal transport and decreases tissue cystine.

-  Oral cysteamine does not achieve adequate levels in ocular tissues, so additional therapy with cysteamine eyedrops is required.

-  Early initiation of the drug can prevent or delay deterioration of renal function.

-  Patients with growth failure that does not improve with cysteamine might benefit from treatment with growth hormone.

-  Kidney transplantation is a viable option in patients with renal failure.

Complications:

With prolonged survival, additional complications may become evident, including:

-       central nervous system abnormalities

-       muscle weakness

-       swallowing dysfunction,

-       ocular cystinosis with eventual blindness,

-       functional nephrogenic diabetes insipidus,proximal RTA

,hypophosphatemic rickets, eventual progression to ESRD,

-       hypothyroidism,

-       pancreatic insufficiency.

N.B: It is unclear whether long-term cysteamine therapy will decrease these complications.

- If left untreated, ESRD is reached by 7–10 years of age in the infantile form